Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Signal processing at the Ras circuit: what shapes Ras activation patterns?

N I Markevich1, G Moehren, O V Demin

  • 1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Systems Biology
|October 21, 2006
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

G Protein-Coupled Receptor Signaling Networks from a Systems Perspective.

Molecular pharmacology·2015
Same author

Amygdalar neuronal plasticity and the interactions of alcohol, sex, and stress.

Brain structure & function·2014
Same author

EI of the Phosphotransferase System of Escherichia coli: Mathematical Modeling Approach to Analysis of Its Kinetic Properties.

Journal of biophysics (Hindawi Publishing Corporation : Online)·2011
Same author

[A kinetic model of beta-galactosidase of Escherichia coli].

Biofizika·2009
Same author

Comparative studies on nicotinamide nucleotide transhydrogenase from different sources.

Biochimica et biophysica acta·2009
Same author

Domain-oriented reduction of rule-based network models.

IET systems biology·2008
Same journal

Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib.

Systems biology·2006
Same journal

Elimination of the initial value parameters when identifying a system close to a Hopf bifurcation.

Systems biology·2006
Same journal

Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways.

Systems biology·2006
Same journal

Direct Lyapunov exponent analysis enables parametric study of transient signalling governing cell behaviour.

Systems biology·2006
Same journal

Systems theory of Smad signalling.

Systems biology·2006
Same journal

STAT module can function as a biphasic amplitude filter.

Systems biology·2006
See all related articles

This study reveals how Ras signaling integrates cellular signals, showing transient RasGAP activation explains sustained Ras-GTP patterns crucial for cell fate and cancer development.

Area of Science:

  • Systems biology
  • Cellular signal transduction
  • Molecular signaling pathways

Background:

  • Ras proteins act as critical molecular switches controlling cell fate.
  • Ras activity is regulated by intrinsic GTPase activity and external signaling factors.
  • Dysregulation of Ras signaling is implicated in various cancers.

Purpose of the Study:

  • To quantitatively understand Ras signaling integration using a systems biology approach.
  • To elucidate the mechanisms underlying sustained Ras-GTP signaling in response to epidermal growth factor (EGF).
  • To investigate the role of Ras GTPase-activating protein (RasGAP) in regulating Ras activity.

Main Methods:

  • Systems biology approach integrating experimental data and kinetic modeling.

Related Experiment Videos

  • Analysis of Ras-GTP levels in hepatocytes stimulated with EGF.
  • Development of a comprehensive kinetic model of the EGF receptor (EGFR) network.

    • Main Results:

    • Basal Ras-GTP levels are highly sensitive to GTP-hydrolysis rates, explaining Ras mutant carcinogenicity.
    • Transient SOS activation and sustained Ras-GTP patterns were observed upon EGF stimulation.
    • Transient RasGAP activation, not just SOS signal switching, is required to explain observed signaling dynamics.
    • A kinetic model incorporating EGFR-mediated recruitment and complex formation of RasGAP with p190 RhoGAP explained hepatocyte data.

    Conclusions:

    • Transient RasGAP activation is a key mechanism for sustained Ras-GTP signaling.
    • The interplay between EGFR, SOS, RasGAP, and p190 RhoGAP regulates cellular signal transduction.
    • Integrated dynamic analysis combined with experimental monitoring can dissect complex signaling networks.